biostudies-literatureMentzer AJMedical Research CouncilNational Institute for Health Research (NIHR)Wellcome TrustAcademy of Medical Sciences147-157https://www.ebi.ac.uk/biostudies/studies/S-EPMC9873562biostudies-literatureUnknown29(1)Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine immunogenicity varies between individuals, and immune responses correlate with vaccine efficacy. Using data from 1,076 participants enrolled in ChAdOx1 nCov-19 vaccine efficacy trials in the United Kingdom, we found that inter-individual variation in normalized antibody responses against SARS-CoV-2 spike and its receptor-binding domain (RBD) at 28 days after first vaccination shows genome-wide significant association with major histocompatibility complex (MHC) class II alleles. The most statistically significant association with higher levels of anti-RBD antibody was HLA-DQB1*06 (P = 3.2 × 10^-9), which we replicated in 1,677 additional vaccinees. Individuals carrying HLA-DQB1*06 alleles were less likely to expeNature medicineHuman leukocyte antigen alleles associate with COVID-19 vaccine immunogenicity and risk of breakthrough infection.PMC9873562203141/Z/16/ZCL-2018-13-007204969/Z/16/Z211153/Z/18/ZSGL024\1096MC_UU_00004/04NIHR201409Ferreira DMHanumunthadu BBull MBMinassian APollard AJFowler JMarchevsky NCifuentes LClutterbuck EAGodfrey LLazarus RO'Connor DAdlou SHill HEmary KRWKarp-Tatham ELi GOxford COVID Vaccine Trial Genetics Study Team GroupShaw RHLambe TTurnbull IFinn AFelle SChong AYKwok JGreen CAHeath PRamasamy MNLibri VBibi SFlaxman ALSanders KStuart AFeng SAlamad BPollock KFaust SNSutherland RKThomson ECWilliams CJABeveridge AChelysheva ILillie PJLiu XSnape MDDarton TMalinauskas TDuncan CJAKhozoee BMentzer AJDinesh TCollins AMToshner MKnight JCProvtsgaard-Morys SVoysey MMakinson RMcGregor ACHart TSmith AEdwards NJTurner DPJGoodman ALPayne ROSmith CCAngus BCicconi PCavey AAnslow RDemissie TfalseHuman leukocyte antigen alleles associate with COVID-19 vaccine immunogenicity and risk of breakthrough infection.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine immunogenicity varies between individuals, and immune responses correlate with vaccine efficacy. Using data from 1,076 participants enrolled in ChAdOx1 nCov-19 vaccine efficacy trials in the United Kingdom, we found that inter-individual variation in normalized antibody responses against SARS-CoV-2 spike and its receptor-binding domain (RBD) at 28 days after first vaccination shows genome-wide significant association with major histocompatibility complex (MHC) class II alleles. The most statistically significant association with higher levels of anti-RBD antibody was HLA-DQB1*06 (P = 3.2 × 10^-9), which we replicated in 1,677 additional vaccinees. Individuals carrying HLA-DQB1*06 alleles were less likely to expe2023-01-01T00:00:00Z2023 Jan2026-05-10T06:54:29.385Z2025-04-07T03:20:15.97ZS-EPMC98735623622865910.1038/s41591-022-02078-6